ESPE Abstracts

Introduction: Denosumab is a RANK-L inhibitory monoclonal antibody approved in adults for treatment of aneurysmal bone cyst (ABC) and giant cell tumor (GCT). Although it has shown to improve postsurgical morbidity and stop progression in unresectable forms, there is limited data to guide its use in growing patients, with reports of endocrinology disorders.

Aim: Evaluate frequency, presentation and treatment of adverse effects in pediatric patients (p) who received Denosumab for ABC and GCT.

Methods: A prospective and descriptive study including p under 18 years old treated with Denosumab at one single center between 2022 to 2024. All p underwent phosphocalcic laboratory test prior to starting treatment and before each dose. Lower limb x-rays were requested in all p.

Outcomes:Six p (4 ABC, 2 CGT) were treated with Denosumab of whom only one continues. The median age at start of treatment (X͂As) was 7.4 years (3.25-15), with a male: female predominance (5:1). One had Noonan Syndrome. All had a very good response, except for one who developed sarcomatous transformation. Before treatment, p initiated calcium supplement 500-1000 mg/day and vitamin D 1000 or 3000 IU/day (prophylaxis or deficiency). Adjustments were made according to the laboratory values prior to each dose. Denosumab regimen was 70 mg/m2/dose, weekly during the first month and then monthly, with a median number of doses of 18 (7-22). During treatment, all p presented hypocalcemia (minimum 7.6 mg/dl) and 3/6 had hypophosphatemia (minimum 1.5 mg/dl), which were managed orally. Post treatment, 3/5 p presented hypercalcemia with a median value of 17 mg/dl (16.4-17) with a median time since last dose of 15 weeks (6-16), and a X͂As of 5.83 years (3.25-9.1). All hypercalcemic p were symptomatic and treated with hyperhydration, furosemide, and bisphosphonates. All p who underwent x-rays and were in a growth period had metaphyseal esclerosis. Compromise of linear growth or fractures were not observed.

Conclusions: Denosumab showed adverse effects both during and after treatment. Hypocalcemia and hypophosphatemia occurred during treatment despite prophylactic measures. Post-treatment, hypercalcemia emerged as the most serious adverse effect requiring aggressive management. Risk factors seem to be younger age, a higher number of doses, and the development of metaphyseal sclerosis. These findings highlight the critical need to implement strategies to prevent post-Denosumab effects.